Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

Bioengineering and in utero transplantation of fetal skin in the sheep model: A crucial step towards clinical application in human fetal spina bifida repair

An intricate problem during open human fetal surgery for spina bifida regards back skin closure, particularly in those cases where the skin defect is much too large for primary closure. We hypothesize that tissue engineering of fetal skin might provide an adequate autologous skin substitute for in utero application in such situations. Eight sheep fetuses of four time‐mated ewes underwent fetoscopic skin biopsy at 65 days of gestation. Fibroblasts and keratinocytes isolated from the biopsy were used to create fetal dermo‐epidermal skin substitutes. These were transplanted on the fetuses by open fetal surgery at 90 days of gestation on skin defects (excisional wounds) created during the same procedure. Pregnancy was allowed to continue until euthanasia at 120 days of gestation. The graft area was analyzed macroscopically and microscopically. The transplanted fetal dermo‐epidermal skin substitutes was well discernable in situ in three of the four fetuses available for analysis. Histology confirmed healed grafts with a close to natural histological skin architecture four weeks after in utero transplantation. This experimental study generates evidence that laboratory grown autologous fetal skin analogues can successfully be transplanted in utero. These results have clinical implications as an analogous procedure might be applied in human fetuses undergoing prenatal repair to facilitate primary skin closure. Finally, this study may also fertilize the field of fetal tissue engineering in general, particularly when more interventional, minimally invasive, and open fetal surgical procedures become available.     

Diagnosing acquired syphilis through oral lesions: the 12 year experience of an Oral Medicine Center

IntroductionA resurgence of syphilis in Brazil has been reported in recent years.ObjectiveWith this in mind, the present study sought to investigate the frequency, demographics, and clinical characteristics of patients with acquired syphilis with oral involvement who received medical care at an Oral Medicine Reference Center in a Brazilian Public Hospital.MethodsA retrospective study, spanning a period of 12 years, was performed to identify changing trends in syphilis over time. Medical records from all patients diagnosed with acquired syphilis who received medical care at the Hospital's Oral Medicine Clinic from 2005 to 2016 were reviewed, and the demographic and clinical data were collected.ResultsA total of 85 patients had been diagnosed with acquired syphilis, with a significant increase in the number of cases over the past 5 years. Patients ranged from 16 to 76 years of age, with a peak in the third and fourth decades. Forty-eight cases affected males (56.5%), while 37 cases affected females (43.5%). Most of the oral lesions appeared as unique ulcers or plaques, with the lips and tongue representing the most affected sites. All cases were positive for Venereal Disease Research Laboratory or Fluorescent Treponemal Antibody Absorption, and treatment was performed with Penicillin G benzathine in most cases (84.7%).ConclusionThe frequency of oral syphilis has been rising over time and oral lesions may well represent a diagnostic clue; therefore, oral health professionals must be made aware and properly trained in an attempt to develop a high degree of clinical suspicion in the diagnosis of syphilis.     

丹银海绵对糖尿病大鼠皮肤溃疡创面愈合的影响

目的:探讨丹银海绵对糖尿病大鼠皮肤溃疡创面愈合的影响。方法:将雄性Wistar大鼠随机分为8组。除空白对照组外,其余7组大鼠,通过手术在其背部形成一10mm×10mm相同大小,深达肌层的溃疡,分别给予抗生素、生长因子凝胶、纳米银、丹黄散,以及不同浓度的丹银海绵处理溃疡面。给药28d后处死大鼠,取溃疡部位新生肉芽组织,HE染色观察组织形态的变化;WesternBlot检测大鼠创面组织中AGEs、hs-CRP、IL-1、IL-6、bFGF、PDGF、VEGF表达水平。结果:病理切片观察显示适宜浓度的丹银海绵可以促进血管新生并伴扩张,同时生成大量新生成纤维细胞。WesternBlot检测显示高浓度的丹银海绵可以显著上调创面组织中生长因子表达(P<0.05),降低AGEs水平及炎症因子表达(P<0.05)。结论:适宜浓度的丹银海绵对于糖尿病大鼠皮肤溃疡的愈合有明显的促进作用,提高治疗效果。     

VAC结合游离植皮治疗儿童大面积皮肤缺损疗效观察及对患儿生活质量的影响

目的:探讨负压创面治疗技术(Vacuum assisted closure,VAC)结合游离植皮治疗儿童大面积皮肤缺损疗效及对患儿生活质量的影响。方法:选取2015年2月-2019年2月笔者医院收治的60例大面积皮肤缺损患儿作为研究对象,按照随机数表法分为干预组和对照组,每组30例。对照组采用游离植皮术治疗,干预组在对照组的基础上结合VAC治疗,以皮片成活时间、皮片成活率、换药次数及住院天数评估疗效,以长海痛尺分级法评估患儿疼痛等级,以抑郁自评量表(Self-rating depression scale,SDS)、焦虑自评量表(Self-rating anxiety scale,SAS)评估患儿心理状态,以术后不良反应发生率评估患儿预后情况,以自制生活质量表评估患儿生活质量水平。结果:干预组患儿皮片成活时间、换药次数与住院天数均小于对照组,差异有统计学意义(P<0.05)。干预组患儿皮片成活率为93.33%高于对照组的76.67%,差异有统计学意义(P<0.05)。干预组治疗后疼痛感、SDS与SAS评分低于治疗前,且低于对照组,差异有统计学意义(P<0.05)。干预组患儿术后不良反应发生率为6.67%显著低于对照组23.33%,差异有统计学意义(P<0.05)。两组治疗前活动能力、心理健康及社交能力均低于治疗后,干预组治疗后活动能力、心理健康及社交能力均高于对照组(P<0.05)。结论:VAC结合游离植皮治疗儿童大面积皮肤缺损疗效显著,能有效降低患儿生理疼痛与心理焦虑,减少伤口感染等不良反应的发生,提高患儿生活质量,具有推广价值。     

Granulomatous/sarcoid-like reactions in the setting of programmed cell death-1 inhibition: a potential mimic of disease recurrence

Nivolumab and pembrolizumab are humanized IgG4 monoclonal antibodies against programmed cell death 1 (PD-1). Although these agents are effective in treating advanced melanoma, non-small-cell lung carcinoma, and other types of cancers, various adverse events have been reported. Cutaneous adverse events are particularly prevalent and, while granulomatous/sarcoid-like reactions are uncommon, they are increasingly recognized as immune-related adverse events associated with immune checkpoint inhibitors. Herein, we report two cases of granulomatous/sarcoid-like reaction with foreign material, mimicking metastatic malignancy after PD-1 inhibitor treatment. Clinicians should be aware of the existence of cutaneous lesions and perform biopsy if needed to prevent misdiagnosis and unnecessary adjustments to immunotherapy.